JANUS under stress - Role of JAK/STAT signaling pathway in vascular diseases
JANUS under stress - Role of JAK/STAT signaling pathway in vascular diseases
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DOI：
10.1016/j.vph.2005.08.021
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发表时间：
2005-11-01
影响因子：
4
通讯作者：
Schieffer, B
中科院分区：
文献类型：
--
作者：
Grote, K;Luchtefeld, M;Schieffer, B
它们不仅仅是另一种激酶（JAK），当它们在80年代末首次被描述并命名为JAK激酶时。这种新的双重活性Janus激酶（JAK）家族及其底物信号转导子和转录激活子（STAT）的强制性作用在缺乏功能等位基因（例如JAK 2）的胚胎发生期间死亡的小鼠中得到证实。最初，JAK/STAT信号通路被发现是造血和免疫细胞中干扰素诱导的细胞内信号传导的主要介质。目前，公认JAK激酶和STAT蛋白以细胞类型特异性方式在血管壁中组成型表达，并传递各种受体家族的细胞内信号传导事件，例如细胞因子、生长因子和血管活性肽如血管紧张素II（Ang II）或内皮素的细胞内信号传导事件。JAK/STAT信号传导途径对心血管病理生理学和疾病发展的潜在影响来自描述JAK可直接结合血管紧张素II I型（AT 1）受体的报道，从而增强其在血管壁的各种细胞类型中的磷酸化。更有趣的是，这些信号传导事件受到NAD（P）H氧化酶衍生的超氧阴离子的调节，这些超氧阴离子直接磷酸化JAK 2，从而控制JAK 2活性。还描述了对动脉粥样硬化斑块发展的潜在影响，其中JAK和STAT的激活似乎是关键的。基于这些观察，我们在这里审查的JAK/STAT信号通路的作用，作为心血管疾病的发展，即动脉粥样硬化斑块的进展或动脉高血压的表现的关键调节器。(c)2005年爱思唯尔公司All rights reserved.
They were more than just another kinases (JAK), when they were first described in the late 80s and named JAK kinases. The mandatory role of this novel family of dual active janus kinases (JAK) and their substrates the signal transducers and activators of transcription (STAT) was demonstrated in mice who died during embryogenesis when lacking a functional allele, e.g. that of JAK2. Initially, the JAK/STAT signaling pathway was discovered as the primary mediator of intracellular signaling induced by interferon in hematopoietic and immune cells. Nowadays, it is well accepted that JAK kinases and STAT proteins are constitutively expressed in the vessel wall in a cell type specific manner and transfer intracellular signaling events of various receptor families, e.g. that of cytokines, growth factors and vasoactive peptides such as angiotensin II (Ang II) or endothelin. The potential impact of the JAK/STAT signaling pathway on cardiovascular pathophysiology and disease development arise from reports describing that JAKs may bind directly to the angiotensin II type I (AT,) receptor, thereby enhancing their phosphorylation in various cell types of the vessel wall. More interestingly, these signaling events are modulated by NAD(P)H oxidase-derived superoxide anions which directly phosphorylate JAK2 and thereby control JAK2 activity. A potential impact was also described for atherosclerotic plaque development in which the activation of JAKs and STATs seems to be critical. Based on these observations, we here review the role of the JAK/STAT signaling pathways as critical regulator for cardiovascular disease development, i.e. atherosclerotic plaque progression or the manifestation of arterial hypertension. (c) 2005 Elsevier Inc. All rights reserved.